Glutamatergic neurotransmission and the active brain neurotransmitter systems support the operation of mechanisms controlling psychoemotional status. Convincing evidence has now been reported on the involvement of brain areas key for regulating emotions, including the prefrontal cortex, hippocampus, nucleus accumbens, ventral tegmental area, serotoninergic raphe nuclei, and amygdala, as well as in the pathogenesis of depression and the therapeutic effects of antidepressants. Impairments to the balance between “excitatory” and “inhibitory” signals to these areas, judging from experimental and clinical data, appear to underlie depressive psychoemotional disorders. Efforts in identifying the mechanisms of depression and antidepressant responses have received significant support because of the development of optogenetic methods and their introduction into research practice. Studies in recent years using optogenetic approaches and the forthcoming translation of their main results into clinical practice are discussed in this review.